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Hypofractionated Irradiation At Regional Nodal Area for Breast Cancer Vs Existed Standard Treatment (HARVEST)

Primary Purpose

Breast Cancer

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Hypofractionated radiotherapy
Conventional radiotherapy
Sponsored by
Ruijin Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring regional nodal irradiation, IMRT, Hypofractionated radiotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion criteria :

  • Age 18-75 years old
  • unilateral histologically confirmed invasive breast carcinoma of pT1-3
  • breast conservation surgery or mastectomy
  • Breast reconstruction is allowed
  • histologically confirmed positive axillary lymph nodes (positive sentinel lymph nodes without axillary dissection is allowed)
  • Life expectancy of >5 years
  • A minimum negative surgical margin width of >2mm
  • Karnofsky Performance Status ≥80
  • Estrogen-receptor, Progesterone-receptor, human epidermal growth factor receptor-2 (HER-2) and Ki67 index can be performed on the primary breast tumor or axillary nodes.
  • Written informed consent

Exclusion criteria:

  • Supraclavicular lymph nodes, positive ipsilateral internal mammary lymph nodes or residual axillary nodes that may be eligible for a boost dose.
  • Pregnant or lactating
  • Severe non-neoplastic medical comorbidities
  • Diagnosis of non-breast malignancy within 5 years preceding enrollment (except for basal cell carcinoma of the skin or carcinoma in situ of the cervix).
  • Simultaneous contralateral breast cancer
  • Previous RT to thoracic and/or axillary, cervical region
  • Active collagen vascular disease
  • Evidence of distant metastatic disease and/or T4 disease

Notes for exlusion criteria:

  1. Patients with severe non-neoplastic medical comorbidities (e.g.,severe ischemic heart disease, severe arrhythmia or severe chronic obstructive pulmonary disease ) that would preclude radiation treatment will be excluded.
  2. Simultaneous contralateral breast cancer includes histologically confirmed DCIS only.

Sites / Locations

  • Ruijin Hospital, Shanghai Jiaotong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Hypofractionated radiotherapy

Conventional radiotherapy

Arm Description

Patients with an indication for regional nodal irradiation will received 2.67 Gy for 16 fractions to chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes) and sequential tumor bed boost of 2.67 Gy for 4 fractions following breast conserving surgery

Patients with an indication for regional nodal irradiation will received 2 Gy for 25 fractions to chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes) and sequential tumor bed boost of 2 Gy for 5 fractions following breast conserving surgery.

Outcomes

Primary Outcome Measures

Locoregional recurrence (LRR)
any first recurrence confirmed by histology or cytology in the ipsilateral chest wall or breast or regional nodes areas (including axillary, supraclavicular, infraclavicular lymph nodes or IMN)

Secondary Outcome Measures

Distant metastasis free survival (DMFS)
the time from the date of randomization to any recurrence of tumor at distant sites or death from any cause.
Invasive recurrence-free survival (IRFS)
the time from the date of randomization to any invasive recurrence of tumor, distant metastases or death from any cause and second invasive primaries, including invasive neoplasms of the breast.
over survival (OS)
the time from the date of randomization to the date of death from any cause or end of the follow-up.
Number of Participants with excellent or good Cosmetic outcomes following breast conserving surgery-Harvard/NSABP/RTOG scoring scale
The time from the date of randomization to 5 years after completion of radiotherapy, the cosmetic outcomes will be evaluated before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter. The cosmetic outcomes are evaluated based on the Allegheny General Modification of the Harvard/(National Surgical Adjuvant Breast and Bowel Project) NSABP/ (Radiation Therapy Oncology Group) RTOG scoring scale which graded patients into the following four classifications: excellent, when compared to the untreated breast, there is a minimal or no difference in the size or shape of the treated breast; good, slight difference in the size or shape of the treated breast; fair, obvious difference in the size or shape of the treated breast; and poor, marked change in the size or shape of the treated breast.
Number of Participants with ≥Grade1 Acute Radiation-induced Toxicity
within time from beginning of RT to 6 months after completion of RT assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Number of Participants with ≥Grade1 Late Radiation-induced Toxicity
within time from 6 months after completion of RT to 5 years after completion of RT assessed according to the RTOG/ European Organization for Research on Treatment of Cancer (EORTC） Late Radiation Morbidity Scoring Schema and CTCAE version 3.0
Reconstruction complications
number of participants with any reconstruction complications (flap necrosis, capsular contracture, infection, loss of implant/expander or flaps, et al) and the interval between the RT and reconstruction complications will be recorded. Patient reported outcome with reconstruction will be evaluated by Breast-Q questionnaires before RT and 12 months after RT.

Full Information

First Posted
January 27, 2019
Last Updated
May 29, 2022
Sponsor
Ruijin Hospital
Collaborators
RenJi Hospital, Shanghai 10th People's Hospital, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Zhongshan Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Affiliated Hospital of Jiangnan University, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China
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1. Study Identification

Unique Protocol Identification Number
NCT03829553
Brief Title
Hypofractionated Irradiation At Regional Nodal Area for Breast Cancer Vs Existed Standard Treatment
Acronym
HARVEST
Official Title
Hypofractionated Versus Conventional Intensity-Modulated Radiation Therapy for Breast Cancer Patients With an Indication for Regional Nodal Irradiation: A Randomized Multi-center Phase III Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 21, 2019 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruijin Hospital
Collaborators
RenJi Hospital, Shanghai 10th People's Hospital, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Zhongshan Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Affiliated Hospital of Jiangnan University, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The main objective of this trial is to investigate the efficacy and safety of hypofractionated radiotherapy of 3 or 4 weeks by comparing with conventional radiotherapy of 5 or 6 weeks using intensity-modulated radiation therapy (IMRT) in breast cancer patients with an indication for regional nodal irradiation (RNI) following mastectomy or breast conserving surgery. Patients will be randomized to hypofractionated radiotherapy or conventional radiotherapy delivered to chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes). Eligible breast cancer patients will be followed for at least 5 years to evaluate the difference in 5-year locoregional recurrence, over survival, distant metastasis, toxicity and life quality between two groups.
Detailed Description
Investigators hypothesize that hypofractionated radiotherapy is equally effective and safe as conventional radiotherapy in breast cancer patients with an indication for regional nodal irradiation. Eligible breast cancer patients are randomized 1:1 into the following two groups: hypofractionated radiotherapy of 2.67 Gy for 16 fractions (and sequential tumor bed boost of 2.67 Gy for 4 fractions in patients with intact breast) and conventional radiotherapy of 2Gy for 25 fractions (and sequential tumor bed boost of 2 Gy for 5 fractions in patients with intact breast). The dose was prescribed to ipsilateral chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes). All patients are treated with IMRT. The primary endpoint is locoregional recurrence. Patients will be followed at least 5 years after radiotherapy to evaluated over survival, distant metastasis, toxicity and life quality.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
regional nodal irradiation, IMRT, Hypofractionated radiotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
801 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hypofractionated radiotherapy
Arm Type
Experimental
Arm Description
Patients with an indication for regional nodal irradiation will received 2.67 Gy for 16 fractions to chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes) and sequential tumor bed boost of 2.67 Gy for 4 fractions following breast conserving surgery
Arm Title
Conventional radiotherapy
Arm Type
Active Comparator
Arm Description
Patients with an indication for regional nodal irradiation will received 2 Gy for 25 fractions to chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes) and sequential tumor bed boost of 2 Gy for 5 fractions following breast conserving surgery.
Intervention Type
Radiation
Intervention Name(s)
Hypofractionated radiotherapy
Other Intervention Name(s)
Experimental Arm
Intervention Description
4005 cGy/ 15 fractions / 3 weeks to ipsilateral chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes) and sequential tumor bed boost of 2.67Gy for 4 fractions in patients with intact breast
Intervention Type
Radiation
Intervention Name(s)
Conventional radiotherapy
Other Intervention Name(s)
Active Comparator Arm
Intervention Description
5000 cGy/ 25 fractions / 5 weeks ipsilateral chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes) and sequential tumor bed boost of 2Gy for 5 fractions in patients with intact breast
Primary Outcome Measure Information:
Title
Locoregional recurrence (LRR)
Description
any first recurrence confirmed by histology or cytology in the ipsilateral chest wall or breast or regional nodes areas (including axillary, supraclavicular, infraclavicular lymph nodes or IMN)
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Distant metastasis free survival (DMFS)
Description
the time from the date of randomization to any recurrence of tumor at distant sites or death from any cause.
Time Frame
5 years
Title
Invasive recurrence-free survival (IRFS)
Description
the time from the date of randomization to any invasive recurrence of tumor, distant metastases or death from any cause and second invasive primaries, including invasive neoplasms of the breast.
Time Frame
5 year
Title
over survival (OS)
Description
the time from the date of randomization to the date of death from any cause or end of the follow-up.
Time Frame
5 years
Title
Number of Participants with excellent or good Cosmetic outcomes following breast conserving surgery-Harvard/NSABP/RTOG scoring scale
Description
The time from the date of randomization to 5 years after completion of radiotherapy, the cosmetic outcomes will be evaluated before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter. The cosmetic outcomes are evaluated based on the Allegheny General Modification of the Harvard/(National Surgical Adjuvant Breast and Bowel Project) NSABP/ (Radiation Therapy Oncology Group) RTOG scoring scale which graded patients into the following four classifications: excellent, when compared to the untreated breast, there is a minimal or no difference in the size or shape of the treated breast; good, slight difference in the size or shape of the treated breast; fair, obvious difference in the size or shape of the treated breast; and poor, marked change in the size or shape of the treated breast.
Time Frame
5 years
Title
Number of Participants with ≥Grade1 Acute Radiation-induced Toxicity
Description
within time from beginning of RT to 6 months after completion of RT assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time Frame
6 months
Title
Number of Participants with ≥Grade1 Late Radiation-induced Toxicity
Description
within time from 6 months after completion of RT to 5 years after completion of RT assessed according to the RTOG/ European Organization for Research on Treatment of Cancer (EORTC） Late Radiation Morbidity Scoring Schema and CTCAE version 3.0
Time Frame
5 years
Title
Reconstruction complications
Description
number of participants with any reconstruction complications (flap necrosis, capsular contracture, infection, loss of implant/expander or flaps, et al) and the interval between the RT and reconstruction complications will be recorded. Patient reported outcome with reconstruction will be evaluated by Breast-Q questionnaires before RT and 12 months after RT.
Time Frame
5 years
Other Pre-specified Outcome Measures:
Title
Quality of Life-EORTC QLQ-C30
Description
The time from the date of randomization to 5 years after completion of radiotherapy, Quality of life will be assessed before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter using self-administered questionnaire EORTC QLQ-C30
Time Frame
1 years
Title
Quality of Life-EORTC QLQ-C30
Description
The time from the date of randomization to 5 years after completion of radiotherapy, Quality of life will be assessed before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter using self-administered questionnaire EORTC QLQ-C30
Time Frame
5 years
Title
Quality of Life-EORTC QLQ-BR23
Description
The time from the date of randomization to 5 years after completion of radiotherapy, Quality of life will be assessed before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter using self-administered questionnaire EORTC QLQ-BR23
Time Frame
1 years
Title
Quality of Life-EORTC QLQ-BR23
Description
The time from the date of randomization to 5 years after completion of radiotherapy, Quality of life will be assessed before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter using self-administered questionnaire EORTC QLQ-BR23
Time Frame
5 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria : Age 18-75 years old unilateral histologically confirmed invasive breast carcinoma of pT1-3 breast conservation surgery or mastectomy Breast reconstruction is allowed histologically confirmed positive axillary lymph nodes (positive sentinel lymph nodes without axillary dissection is allowed) Life expectancy of >5 years A minimum negative surgical margin width of >2mm Karnofsky Performance Status ≥80 Estrogen-receptor, Progesterone-receptor, human epidermal growth factor receptor-2 (HER-2) and Ki67 index can be performed on the primary breast tumor or axillary nodes. Written informed consent Exclusion criteria: Supraclavicular lymph nodes, positive ipsilateral internal mammary lymph nodes or residual axillary nodes that may be eligible for a boost dose. Pregnant or lactating Severe non-neoplastic medical comorbidities Diagnosis of non-breast malignancy within 5 years preceding enrollment (except for basal cell carcinoma of the skin or carcinoma in situ of the cervix). Simultaneous contralateral breast cancer Previous RT to thoracic and/or axillary, cervical region Active collagen vascular disease Evidence of distant metastatic disease and/or T4 disease Notes for exlusion criteria: Patients with severe non-neoplastic medical comorbidities (e.g.,severe ischemic heart disease, severe arrhythmia or severe chronic obstructive pulmonary disease ) that would preclude radiation treatment will be excluded. Simultaneous contralateral breast cancer includes histologically confirmed DCIS only.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jia-Yi Chen
Phone
+86-021-64370045
Ext
602400
Email
chenjiayi0188@aliyun.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jia-Yi Chen
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jia-Yi Chen, M.D.
Phone
+86-021-64370045
Ext
602400
Email
chenjiayi0188@aliyun.com
First Name & Middle Initial & Last Name & Degree
Jia-Yi Chen, M.D
Phone
+86-021-64370045
Ext
602400
Email
chenjiayi0188@aliyun.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Hypofractionated Irradiation At Regional Nodal Area for Breast Cancer Vs Existed Standard Treatment

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